Editorial Comment 6/4: Rebuttal to guest editorial

Editorial Comment:  Rebuttal to guest editorial

(Dr. Stuart Gitlow’s guest editorial, titled “End-point in AUD Treatment” and posted 26 February 2019, followed comments reported from Dr. Raymond Anton and colleagues in the December 2018 AAAP meeting, in Clinical Psychiatry News dated 21 February:   https://www.mdedge.com/psychiatry/article/194926/addiction-medicine/alcohol-abstinence-questioned-addiction-treatment-goal?channel=174&utm_source=News_MDedge_eNL_022219_B&utm_medium=email&utm_content=Abstinence%20questioned%20as%20alcohol%20treatment%20%7C%20Gout%20drug%20hit%20with%20black%20box%20%7C%20And%20more  Dr. Anton’s response follows below.  As is customary, Dr. Gitlow will have the final response, which will be posted in the next (11 June) ASAM Weekly. – WFH3)

Response to Dr. Gitlow regarding use of the WHO risk drinking reduction to guide medication-based treatments.

In a recent guest editorial, Dr. Stuart Gitlow expresses some concerns about a proposed new AUD clinical trial efficacy outcome measure based upon reductions in World Health Organization (WHO) risk drinking levels. The editorial suggests more broadly that “reductions in alcohol use” are not an adequate measure of recovery from AUD, as they may reflect only a reduction in symptoms (that is alcohol related pathology).  As such, he contends there is a confound between the disease of AUD and its symptoms or consequences, in essence stating that a reduction in drinking and its consequent symptoms are not indicators that the disease is “cured”. As such, an example is given in which a reduction in drinking might be equivalent to symptomatic treatment of “cough” in patients with tuberculosis - such that, despite the patient feeling better (no cough), the course of the disease is not meaningfully changed.  The editorial also mentions that the data from the COMBINE Study, used to evaluate the meaning and utility of the WHO risk drinking levels, are limited because the study AUD sample was not “severely affected”, and the follow-up period was for only one year.

We are happy that Dr. Gitlow attended to our work and provided thoughtful comments for discussion. We also appreciate the opportunity to respond to what we believe are arguable and clarifying points.  First, we find the analogy with tuberculosis to be a bit unfortunate as it equates a symptom of an infectious disease (i.e., cough) with a reduction in drinking in AUD. The analogy is a bit flawed because, unlike the “cough in tuberculosis”, “drinking in AUD” is not just a symptom but also a cause of the disease (more like the bacillus in TB); and thus, reducing drinking is more likely to impact the course of the AUD process, than treating the cough in tuberculosis is to cure it. Of note, prior to the advent of appropriate antibiotic therapy, TB patients were confined to sanitarium, a socio-behavioral solution compensating for a lack of a “biological cure”. While total abstinence could be considered a “cure for AUD”, it is also possible that as we unravel the brain etiology and neuroscience of AUD, medications (analogous to antibiotics for TB) will someday result in “cures”.  In the meantime, medications can, and do, reduce alcohol-intake leading to improvements in disease symptoms including such things as improved blood pressure, liver function, as well as social functioning.  As such, AUD is more analogous to other chronic diseases, such as hypertension and Type II diabetes, that are driven by both biological parameters and health behaviors. The absence of a “cure” for these diseases requires that they be treated carefully and managed over time, with modifications in both biological mechanisms with medication, as well as change in health behaviors, potentially resulting in lasting improvements in patient health and functioning. Although we do not argue that reduction in drinking with medications is a “cure” for AUD, these reductions can bring about meaningful improvements in health and functioning, particularly if clinically coupled with behavioral change. What we do suggest, however, is that the WHO risk drinking category reduction can meaningfully measure that improvement, and, therefor, can be used to measure meaningful clinical improvement.

A broader issue that underlies the editorial is the notion that “abstinence is the only acceptable outcome for individuals with AUD” particularly for those who are the most “severe”. While alcohol consumption is a necessary condition for an individual to develop an AUD and individuals with AUD who remain abstinent will, at some point, no longer meet criteria for an AUD – typically only 20% of individuals in AUD clinical trials achieve that goal. Also, the majority of AUD individuals, are not those “severely” affected.  In addition, data derived from many NIAAA-funded clinical trials suggest that most AUD individuals seeking outpatient treatment find a “reduction in drinking goal” as the only acceptable option, even if abstinence is recommended. Therefore, taking a patient-centered personalized approach to treating AUD, including both abstinence and efforts to promote reduced drinking, perhaps in a step-wise manner, may be more acceptable to many patients and providers, thereby helping to remedy the well-documented low rate of treatment utilization among individuals with AUD in the general population.

Recent work by the public-private partnership, Alcohol Clinical Trials Initiative (ACTIVE) group (referenced in Dr. Gitlow’s editorial), has shown that reductions in WHO risk drinking levels are associated with reductions in alcohol-related consequences and health care costs, exemplified by improvements in mental health, physical health, and quality of life.  Such reductions in drinking levels are also associated with a lower risk of developing alcohol dependence and drug use disorders with many patients maintaining these reductions for up to three years following treatment. As the editorial noted, the COMBINE Study, while typical of modern clinical trials for including specific drinking entry criteria, may not have captured the full spectrum of the AUD disease. However, patients in the COMBINE Study had significant severity and impairment (e.g., on average drinking 9 drinks per day at baseline [12 drinks per drinking day] and meeting 5 of 7 DSM-IV criteria for alcohol dependence) – similar to many clinical outpatient treatment-seekers. We agree with Dr. Gitlow that to further validate the predictive utility of WHO risk drinking level reductions requires longer-term follow-up in other studies, and that work is currently underway.  In addition to the effects identified to date in the COMBINE Study, the WHO risk drinking approach has been validated in clinical trials in Europe and in the U.S. nationally representative National Epidemiological Survey on Alcohol and Related Conditions (NESARC).  In summary, while a reduced drinking outcome may not be suitable for all patients, we believe that a reduction in WHO risk drinking levels offers an additional medication-assisted treatment goal to abstinence for a substantial proportion of patients with AUD, encouraging them to seek the treatment they might otherwise avoid, or reject, thus broadening the options for this underserved population.

Raymond F. Anton, MD

Katie Witkiewitz, PhD

Henry R. Kranzler, MD

Stephanie S. O’Malley, PhD

Deborah S. Hasin, PhD

As members of the Alcohol Clinical Trials Initiative (ACTIVE) workgroup.

- William Haning, MD, DFAPA, DFASAM